We propose to determine what clinical characteristics, histologic features and molecular and genetic profiles[unreadable] are associated with elevated breast density and with increased risk of invasive breast cancer.[unreadable] Three large, well characterized study cohorts will be used to develop and test this model: (1) 600 women[unreadable] that have undergone mammography and breast biopsies with a benign diagnosis from 2006-9 at the[unreadable] University of California, San Francisco (UCSF) or California Pacific Breast Health Center (CPMC) in San[unreadable] Francisco; (2) 1500 women selected from a cohort of women with benign breast disease (BBD) from 1967-[unreadable] 1992 at the Mayo Clinic whose tissue has been collected and follow-up conducted to determine cancer[unreadable] status, and (3) 400 women that will have undergone screening mammography between 2006-7 at the UCSF[unreadable] Mt. Zion Breast Health Center.[unreadable] We will determine the following: (1) if histologic features (percentage fat, collagen, and epithelium) and a[unreadable] defined set of molecular and genetic characteristics associated with increased mammographic or[unreadable] compositional breast density and breast cancer risk identified in Project 2 [remodelled collagen, insulin-like[unreadable] growth factor binding proteins, cyclooxygenase (COX-2) are associated with extent of breast density[unreadable] measured as mammographic density, volumetric breast density, and compositional density among women[unreadable] with BBD, (2) if clinical characteristics, histologic features (percentage fat, collagen, and epithelium) and[unreadable] molecular and genetic characteristics of benign breast tissue correlated with increased breast density in[unreadable] Specific Aim #1 predict risk of breast cancer, type of invasive breast cancer (ER+ versus ER-), or time to[unreadable] development of cancer, and (3) if women with the 6A allele of TGFBR1 have increased breast density and[unreadable] those homozygous for the P(10) allele of TGF-b1 have decreased breast density and whether haplotypes at the[unreadable] TGF-b1 locus affect the extent of breast density.[unreadable] The results of these studies will provide information on what histologic characteristic and molecular and[unreadable] genetic profile contribute to increased breast density and risk of breast cancer, which may allow[unreadable] identification of a more precise measure of breast cancer risk.